2021
Platelet-derived growth factor receptor beta activates Abl2 via direct binding and phosphorylation
Wu K, Wu H, Lyu W, Kim Y, Furdui CM, Anderson KS, Koleske AJ. Platelet-derived growth factor receptor beta activates Abl2 via direct binding and phosphorylation. Journal Of Biological Chemistry 2021, 297: 100883. PMID: 34144039, PMCID: PMC8259415, DOI: 10.1016/j.jbc.2021.100883.Peer-Reviewed Original ResearchConceptsAbl family kinasesFamily kinasesPlatelet-derived growth factor receptor betaGrowth factor receptor betaAbl familySrc homology 2 domainSrc homology 3 domainDiverse cellular stimuliPost-translational modificationsN-terminal halfNonreceptor tyrosine kinaseMultiple novel sitesAutoinhibited conformationSrc homologyCytoskeleton organizationCytoplasmic domainCellular stimuliKinase domainGrowth factor receptorReceptor betaKinase activityMolecular mechanismsTyrosine kinaseDirect bindingKinaseAbl2:Cortactin Interactions Regulate Dendritic Spine Stability via Control of a Stable Filamentous Actin Pool
Shaw JE, Kilander MBC, Lin YC, Koleske AJ. Abl2:Cortactin Interactions Regulate Dendritic Spine Stability via Control of a Stable Filamentous Actin Pool. Journal Of Neuroscience 2021, 41: 3068-3081. PMID: 33622779, PMCID: PMC8026353, DOI: 10.1523/jneurosci.2472-20.2021.Peer-Reviewed Original ResearchConceptsDendritic spine stabilityDendritic spinesSpine stabilityTonic increaseSubset of spinesSexes of miceMost excitatory synapsesCortactin interactionsGluN2B levelsSpine densitySpine lossArg nonreceptor tyrosine kinaseKinetically distinct poolsExcitatory synapsesHippocampal neuronsSynaptic activitySpine enlargementSpineSpine sizeSpine actinActivity-dependent spine enlargementSpine shapeStructural plasticityDistinct poolsTyrosine kinase
2020
Crystal structure of a guanine nucleotide exchange factor encoded by the scrub typhus pathogen Orientia tsutsugamushi
Lim C, Berk JM, Blaise A, Bircher J, Koleske AJ, Hochstrasser M, Xiong Y. Crystal structure of a guanine nucleotide exchange factor encoded by the scrub typhus pathogen Orientia tsutsugamushi. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 30380-30390. PMID: 33184172, PMCID: PMC7720168, DOI: 10.1073/pnas.2018163117.Peer-Reviewed Original ResearchConceptsBacterial GEFStructure-guided mutational analysisExchange factor domainRho family GTPasesObvious sequence similarityRho GTPases Rac1Pathogen Orientia tsutsugamushiAlters cell morphologyInteraction screenConvergent evolutionGEF domainHost interactorsExchange factorNucleotide displacementGEF activityCellular processesSequence similarityCytoskeletal structuresGTPases Rac1Ectopic expressionMutational analysisGEFRac1Factor domainPathogenic bacterium
2019
Regulation of MT dynamics via direct binding of an Abl family kinase
Hu Y, Lyu W, Lowery LA, Koleske AJ. Regulation of MT dynamics via direct binding of an Abl family kinase. Journal Of Cell Biology 2019, 218: 3986-3997. PMID: 31699690, PMCID: PMC6891085, DOI: 10.1083/jcb.201812144.Peer-Reviewed Original ResearchConceptsAbl family kinasesC-terminal halfFamily kinasesMT dynamicsMT growthTubulin C-terminal tailsC-terminal tailStable reexpressionEssential regulatorCell shapeBinds microtubulesMT polymerizationAbl kinaseGenetic studiesDirect bindingFunctional interactionKinaseMicrotubulesABL2ReexpressionMT behaviorBindingRegulatorProteinGrowth
2018
Abl2 is recruited to ventral actin waves through cytoskeletal interactions to promote lamellipodium extension
Zhang K, Lyu W, Yu J, Koleske AJ. Abl2 is recruited to ventral actin waves through cytoskeletal interactions to promote lamellipodium extension. Molecular Biology Of The Cell 2018, 29: 2863-2873. PMID: 30256707, PMCID: PMC6249870, DOI: 10.1091/mbc.e18-01-0044.Peer-Reviewed Original ResearchConceptsCytoskeletal interactionsLamellipodium extensionTotal internal reflection fluorescence microscopyActin-rich structuresActin wavesActin-rich protrusionsN-terminal halfC-terminal halfNonreceptor tyrosine kinaseReflection fluorescence microscopyFoci colocalizeComplementation analysisLamellipodia protrusionKnockout cellsLamellipodium tipActin filament stabilizerCell shapeBind actinTyrosine kinaseCortactinABL2Fluorescence microscopyIntegrin β3High spatiotemporal resolutionPaxillinCortactin stabilization of actin requires actin-binding repeats and linker, is disrupted by specific substitutions, and is independent of nucleotide state
Scherer AN, Anand NS, Koleske AJ. Cortactin stabilization of actin requires actin-binding repeats and linker, is disrupted by specific substitutions, and is independent of nucleotide state. Journal Of Biological Chemistry 2018, 293: 13022-13032. PMID: 29929984, PMCID: PMC6109930, DOI: 10.1074/jbc.ra118.004068.Peer-Reviewed Original ResearchConceptsHematopoietic cell-specific Lyn substrate 1Nucleotide stateActin bindingActin filamentsTotal internal reflection fluorescence microscopyActin-binding proteins cortactinActin cosedimentation assaysActin-rich structuresHigh-affinity actin bindingADP-actin filamentsReflection fluorescence microscopyAdjacent linker regionActin filament bindingArp2/3 complexCortactin repeatsCellular functionsActin stabilityCosedimentation assaysActin stabilizationProtein cortactinLamellipodial protrusionGTPase regulatorFilament depolymerizationLinker regionActin depolymerization
2014
Abl2/Abl-related Gene Stabilizes Actin Filaments, Stimulates Actin Branching by Actin-related Protein 2/3 Complex, and Promotes Actin Filament Severing by Cofilin*
Courtemanche N, Gifford SM, Simpson MA, Pollard TD, Koleske AJ. Abl2/Abl-related Gene Stabilizes Actin Filaments, Stimulates Actin Branching by Actin-related Protein 2/3 Complex, and Promotes Actin Filament Severing by Cofilin*. Journal Of Biological Chemistry 2014, 290: 4038-4046. PMID: 25540195, PMCID: PMC4326814, DOI: 10.1074/jbc.m114.608117.Peer-Reviewed Original ResearchTwo Amino Acid Residues Confer Different Binding Affinities of Abelson Family Kinase Src Homology 2 Domains for Phosphorylated Cortactin*
Gifford SM, Liu W, Mader CC, Halo TL, Machida K, Boggon TJ, Koleske AJ. Two Amino Acid Residues Confer Different Binding Affinities of Abelson Family Kinase Src Homology 2 Domains for Phosphorylated Cortactin*. Journal Of Biological Chemistry 2014, 289: 19704-19713. PMID: 24891505, PMCID: PMC4094080, DOI: 10.1074/jbc.m114.556480.Peer-Reviewed Original ResearchConceptsAbl SH2 domainSH2 domainAbl family kinasesFamily kinasesSrc homology 2 domainCell edge protrusionAbl SH2Similar N-terminal sequencesImportant non-redundant rolesWild-type levelsAmino acid sequenceAmino acid positionsN-terminal sequenceNon-redundant roleCell morphogenesisArg substrateCellular functionsSpecific phosphotyrosineCell peripheryAcid sequenceSerine 187Edge protrusionTarget proteinsType levelsDifferent binding affinitiesAbelson phosphorylation of CLASP2 modulates its association with microtubules and actin
Engel U, Zhan Y, Long JB, Boyle SN, Ballif BA, Dorey K, Gygi SP, Koleske AJ, VanVactor D. Abelson phosphorylation of CLASP2 modulates its association with microtubules and actin. Cytoskeleton 2014, 71: 195-209. PMID: 24520051, PMCID: PMC4054870, DOI: 10.1002/cm.21164.Peer-Reviewed Original ResearchMeSH KeywordsActin CytoskeletonActinsAmino Acid SequenceAnimalsCell AdhesionChlorocebus aethiopsCOS CellsGrowth ConesHEK293 CellsHumansMicrotubule-Associated ProteinsMicrotubulesMolecular Sequence DataPhosphorylationPhosphotyrosinePlatelet-Derived Growth FactorProtein BindingProto-Oncogene Proteins c-ablSignal TransductionSubcellular FractionsSubstrate SpecificityXenopusConceptsAbelson non-receptor tyrosine kinasesNon-receptor tyrosine kinaseBona fide substrateF-actin structuresVertebrate cellsFide substrateProtein CLASPInteraction domainPDGF stimulationCLASP2Tyrosine residuesF-actinTyrosine kinaseNeural developmentAbl phosphorylationMicrotubulesPhosphorylationGrowth conesCytoskeletonABLFunctional relationshipDrosophilaMultiple stagesKinaseNeurulation
2013
β1 integrin regulates Arg to promote invadopodial maturation and matrix degradation
Beaty BT, Sharma VP, Bravo-Cordero JJ, Simpson MA, Eddy RJ, Koleske AJ, Condeelis J. β1 integrin regulates Arg to promote invadopodial maturation and matrix degradation. Molecular Biology Of The Cell 2013, 24: 1661-1675. PMID: 23552693, PMCID: PMC3667720, DOI: 10.1091/mbc.e12-12-0908.Peer-Reviewed Original ResearchMeSH KeywordsActin Depolymerizing FactorsActinsCell Line, TumorCell MovementCortactinExtracellular MatrixGene Expression Regulation, NeoplasticHumansIntegrin beta1PhosphorylationProtein BindingProtein MultimerizationProtein-Tyrosine KinasesPseudopodiaRNA, Small InterferingSignal TransductionTyrosineConceptsΒ1 integrinBarbed end formationInvasive membrane protrusionsMatrix degradationΒ1 integrin activationMature invadopodiaInvadopodial functionMetastatic human breast cancer cellsMembrane protrusionsExtracellular matrix degradationCortactin phosphorylationTyrosine 421InvadopodiaIntegrin activationMatrix proteolysisHuman breast cancer cellsThree-dimensional matrixPrecursor maturationBreast cancer cellsMetastatic tumor cellsIntegrinsCancer cellsPhosphorylationMaturationFundamental role
2012
Arg/Abl2 Modulates the Affinity and Stoichiometry of Binding of Cortactin to F‑Actin
MacGrath SM, Koleske AJ. Arg/Abl2 Modulates the Affinity and Stoichiometry of Binding of Cortactin to F‑Actin. Biochemistry 2012, 51: 6644-6653. PMID: 22849492, PMCID: PMC3556572, DOI: 10.1021/bi300722t.Peer-Reviewed Original ResearchConceptsStoichiometry of bindingF-actinTerminal calponin homology domainRecruitment of cortactinActin cosedimentation assaysArp2/3 complex activatorsCell edge protrusionActin network assemblyCalponin homology domainProtein-protein interactionsCortactin bindsHomology domainActin cytoskeletonArg CDeletion mutantsCosedimentation assaysFilamentous actinEdge protrusionComplex activatorActin binding propertiesCortactinActin filamentsNetwork assemblyDownstream effectsBindingIntegrin β1 Signals through Arg to Regulate Postnatal Dendritic Arborization, Synapse Density, and Behavior
Warren MS, Bradley WD, Gourley SL, Lin YC, Simpson MA, Reichardt LF, Greer CA, Taylor JR, Koleske AJ. Integrin β1 Signals through Arg to Regulate Postnatal Dendritic Arborization, Synapse Density, and Behavior. Journal Of Neuroscience 2012, 32: 2824-2834. PMID: 22357865, PMCID: PMC3313657, DOI: 10.1523/jneurosci.3942-11.2012.Peer-Reviewed Original ResearchMeSH KeywordsAlpha-FetoproteinsAnalysis of VarianceAnimalsAnimals, NewbornAvoidance LearningBasic Helix-Loop-Helix Transcription FactorsCells, CulturedCocaineDendritesEnzyme-Linked Immunosorbent AssayExploratory BehaviorGreen Fluorescent ProteinsGTPase-Activating ProteinsHippocampusImmunoprecipitationIntegrin beta1MaleMiceMice, KnockoutMutationNerve Tissue ProteinsNeuronsOrgan Culture TechniquesPost-Synaptic DensityProtein BindingRecognition, PsychologyRepressor ProteinsSignal TransductionSrc Homology DomainsSynapsesConceptsIntegrin β1Vertebrate nervous systemExtracellular matrix receptorsGenetic experimentsIntracellular tailGenetic manipulationRhoA GTPaseArg kinaseMatrix receptorsProper hippocampal functionProper developmentSynapse maintenanceDose-sensitive mannerImpaired hippocampus-dependent learningHippocampal dendritic arborsHippocampal synapse lossDendritic arbor sizeHippocampus-dependent learningΒ1ArgSelective lossGTPaseP190RhoGAPPsychomotor sensitivityKinaseLysozyme contamination facilitates crystallization of a heterotrimeric cortactin–Arg–lysozyme complex
Liu W, MacGrath SM, Koleske AJ, Boggon TJ. Lysozyme contamination facilitates crystallization of a heterotrimeric cortactin–Arg–lysozyme complex. Acta Crystallographica Section F: Structural Biology Communications 2012, 68: 154-158. PMID: 22297987, PMCID: PMC3274391, DOI: 10.1107/s1744309111056132.Peer-Reviewed Original ResearchConceptsCrystal structure determinationNonreceptor tyrosine kinaseArg nonreceptor tyrosine kinaseHeterotrimeric complexSH3 domainMacromolecular crystallographersCrystallography approachStructure determinationTyrosine kinaseCocrystal structureMolecular replacementTrace amountsLysozyme complexStructure solutionProteinCortactinComplexesCrystallizationCrystallographersCocrystalsKinaseMotifAutomatic model buildingSequenceArg
2010
Specific tyrosine phosphorylation sites on cortactin regulate Nck1-dependent actin polymerization in invadopodia
Oser M, Mader CC, Gil-Henn H, Magalhaes M, Bravo-Cordero JJ, Koleske AJ, Condeelis J. Specific tyrosine phosphorylation sites on cortactin regulate Nck1-dependent actin polymerization in invadopodia. Journal Of Cell Science 2010, 123: 3662-3673. PMID: 20971703, PMCID: PMC3037016, DOI: 10.1242/jcs.068163.Peer-Reviewed Original ResearchConceptsTyrosine phosphorylation sitesTumor cell invasionActin polymerizationPhosphorylation sitesCell invasionTyrosine 421Actin barbed endsPhosphorylation of tyrosineRegulatory switchSH2 domainMembrane protrusionsInvadopodiaCrucial residuesCortactinBarbed endsDirect bindingInvasive carcinoma cellsPhosphorylationNck1Carcinoma cellsFRET interactionsInvasionCellsPhosphotyrosineSites
2008
Enhancement of ABL Kinase Catalytic Efficiency by a Direct Binding Regulator Is Independent of Other Regulatory Mechanisms*
Cao X, Tanis KQ, Koleske AJ, Colicelli J. Enhancement of ABL Kinase Catalytic Efficiency by a Direct Binding Regulator Is Independent of Other Regulatory Mechanisms*. Journal Of Biological Chemistry 2008, 283: 31401-31407. PMID: 18796434, PMCID: PMC2581583, DOI: 10.1074/jbc.m804002200.Peer-Reviewed Original ResearchConceptsSH2 domainKinase activityTyrosine kinaseAbl family tyrosine kinasesKinase activation mechanismRelief of autoinhibitionUnique protein structureFamily tyrosine kinasesCatalytic site mutationsPhosphorylation of CrkInhibitor-resistant mutantsAbl kinase activityTyrosine kinase activitySH3-SH2ABL tyrosine kinase activityABL2 kinaseABL substratesRegulatory domainPhosphorylation mechanismDownstream effectorsDomain coreInactive conformationAbl SH3Regulatory mechanismsProtein structureThe c-Abl tyrosine kinase regulates actin remodeling at the immune synapse
Huang Y, Comiskey EO, Dupree RS, Li S, Koleske AJ, Burkhardt JK. The c-Abl tyrosine kinase regulates actin remodeling at the immune synapse. Blood 2008, 112: 111-119. PMID: 18305217, PMCID: PMC2435682, DOI: 10.1182/blood-2007-10-118232.Peer-Reviewed Original ResearchMeSH KeywordsActinsAdaptor Proteins, Signal TransducingAnimalsCells, CulturedHumansInterleukin-2Jurkat CellsLymphocyte ActivationMiceMice, KnockoutPhosphorylationProtein BindingProteinsProto-Oncogene Proteins c-ablPseudopodiaReceptors, Antigen, T-CellSignal TransductionT-LymphocytesTranscription, GeneticWiskott-Aldrich Syndrome Protein FamilyConceptsC-AblImmune synapseActin responseC-Abl nonreceptor tyrosine kinaseT cell activationTyrosine kinaseC-Abl tyrosine kinaseC-Abl bindsActin regulatory proteinsNonreceptor tyrosine kinaseChemokine-induced T cell migrationT cell receptor engagementSH2 domainActin dynamicsActin reorganizationTyrosine phosphorylationRegulatory proteinsActin polymerizationDownstream eventsNormal localizationConditional knockout miceCoordinate actionReceptor engagementKinaseLamellipodial spreading
2006
Integrin Signaling through Arg Activates p190RhoGAP by Promoting Its Binding to p120RasGAP and Recruitment to the Membrane
Bradley WD, Hernández SE, Settleman J, Koleske AJ. Integrin Signaling through Arg Activates p190RhoGAP by Promoting Its Binding to p120RasGAP and Recruitment to the Membrane. Molecular Biology Of The Cell 2006, 17: 4827-4836. PMID: 16971514, PMCID: PMC1635390, DOI: 10.1091/mbc.e06-02-0132.Peer-Reviewed Original ResearchConceptsCell peripheryP120 bindingGene Tyrosine KinaseRho family GTPases RhoAActin stress fibersIntegrin-mediated adhesionWild-type fibroblastsP190 phosphorylationFocal adhesionsGTPases RhoARho activityStress fibersEssential effectorTyrosine kinaseAdhesive environmentCell attachmentP190P120P190RhoGAPP120RasGAPPhosphorylationComplex formationBindingRecruitmentRho
2004
The Arg Non-receptor Tyrosine Kinase Modifies F-actin Structure
Galkin VE, Orlova A, Koleske AJ, Egelman EH. The Arg Non-receptor Tyrosine Kinase Modifies F-actin Structure. Journal Of Molecular Biology 2004, 346: 565-575. PMID: 15670605, DOI: 10.1016/j.jmb.2004.11.078.Peer-Reviewed Original ResearchConceptsSubdomain 1Domain bindsActin filamentsF-actinSingle particle image analysisActin-bundling activityNon-receptor tyrosine kinaseCalponin homology domainActin-binding domainF-actin structuresActin subdomain 1Homology domainAbl familyCH domainCell motilityAdjacent protomersTyrosine kinaseParticle image analysisActin protomersConformational changesCooperative bindingARG proteinProtomersArgProteinThe Abl-related gene (Arg) requires its F-actin–microtubule cross-linking activity to regulate lamellipodial dynamics during fibroblast adhesion
Miller AL, Wang Y, Mooseker MS, Koleske AJ. The Abl-related gene (Arg) requires its F-actin–microtubule cross-linking activity to regulate lamellipodial dynamics during fibroblast adhesion. Journal Of Cell Biology 2004, 165: 407-420. PMID: 15138293, PMCID: PMC2172189, DOI: 10.1083/jcb.200308055.Peer-Reviewed Original ResearchConceptsLamellipodial dynamicsCross-linking activityF-actin-binding domainFluorescent protein fusionsMT-binding domainNonreceptor tyrosine kinaseFilamentous actin bundlesWild-type fibroblastsCell polarityProtein fusionsMembrane protrusionsCell peripheryLamellipodial protrusionCell protrusionsActin bundlesMolecular mechanismsTyrosine kinaseF-actinMicrotubulesArgFibroblast adhesionABLHigh affinityFibroblastsProtrusion
2001
The Abl-related gene (Arg) nonreceptor tyrosine kinase uses two F-actin-binding domains to bundle F-actin
Wang Y, Miller A, Mooseker M, Koleske A. The Abl-related gene (Arg) nonreceptor tyrosine kinase uses two F-actin-binding domains to bundle F-actin. Proceedings Of The National Academy Of Sciences Of The United States Of America 2001, 98: 14865-14870. PMID: 11752434, PMCID: PMC64950, DOI: 10.1073/pnas.251249298.Peer-Reviewed Original ResearchMeSH Keywords3T3 CellsActinsAnimalsMiceMicroscopy, ElectronProtein BindingProtein-Tyrosine KinasesRecombinant Fusion ProteinsConceptsF-actin-binding domainActin-rich structuresAbl family kinasesNonreceptor tyrosine kinaseF-actinActin cytoskeletonFamily kinasesFluorescent protein fusion proteinTyrosine kinaseActin-bundling activityProtein fusion proteinActin cytoskeletal structuresCellular morphogenesisSwiss 3T3 fibroblastsBundling activityDeletion mutantsCytoskeletal structuresC-terminusFusion proteinFunctional interactionKinaseActin moleculesCytoskeletonPositive cooperativityArg